The invention relates to cardiology, and more particularly relates to diagnosis of diseases of the myocardium. In its most immediate sense, the invention relates to diagnosis of myocardial disease using magnetic resonance imaging (MRI).
Physicians recognize three distinct categories in which myocardial tissue may be classified. One of these is "normal". "Normal" myocardial tissue is living tissue that is capable of normal movement during the normal expansion and contraction of the heart during the cardiac cycle. For the purposes of this patent application, the determination whether myocardial tissue is normal is made when the patient is at rest.
Another category of myocardial tissue is "injured" tissue that does not move normally during the cardiac cycle. This category includes tissue that is poorly perfused ("ischemic"), and also includes tissue that may be "stunned" and temporarily dysfunctional as a result of an earlier ischemic event.
Finally, myocardial tissue can be categorized as "infarcted". Infarcted tissue is dead. It cannot be treated or brought to life again. As used herein, "infarcted" myocardium includes acutely necrotic myocardium and scar tissue that eventually replaces acutely necrotic myocardium.
When a physician has diagnosed a patient as having ischemic heart disease, it is important to know whether the myocardium is injured or infarcted, and where. Once the existence and extent of injury and/or infarction has been determined, the physician can decide whether e.g. to treat the patient with drugs or whether to carry out a surgical intervention.
Physicians often use myocardial radionuclide studies to help make this determination. A myocardial radionuclide study is a technique whereby the patient's blood is radiolabelled using a radioisotope of a type that is taken up by myocardial tissue (e.g. Thallium). The patient's heart is then imaged using a scintillation camera in a nuclear medicine or positron emission tomography ("PET") study. If a particular region of the myocardium takes up the radioisotope, that region is assumed to contain living tissue; if not, the region is assumed to contain infarcted tissue. However, because both perfusion and viability are necessary for uptake, it may be difficult to distinguish the relative contributions that ischemia and infarction make to the defect.
Nuclear medicine studies also have very poor spatial resolution. As a result, such studies do not precisely show where tissue is dead, where tissue is injured, and where tissue is normal. Furthermore, nuclear medicine studies may take a long time (a conventional multi-scan myocardial radionuclide study may require five hours or more including the time between scans). MRI studies, on the other hand, have excellent spatial resolution and can be completed quickly (in, e.g., less than one hour), but such studies have not heretofore been able to distinguish between normal, injured, and infarcted myocardial tissue.
It would be advantageous to provide a methodology that would permit a physician to distinguish between normal, injured, and infarcted myocardial tissue, with a high degree of spatial resolution.
It would also be advantageous to provide a methodology that would permit such a distinction to be drawn in a study of relatively short duration.
It is therefore one object of the invention to provide methodology whereby a physician can identify infarcted myocardial tissue with a high degree of spatial resolution.
Another object is to provide methodology to distinguish between normal, injured, and infarcted myocardial tissue using a study having a comparatively rapid duration.
Another object is, in general, to improve on known methodology of this general type.
The invention proceeds from a discovery that Gadolinium (Gd) based MR contrast agents (such as Gd-DTPA, which is a chelate of Gadolinium that is known to be an untargeted MR contrast agent preferentially hyperenhance infarcted myocardial tissue after the passage of a predetermined interval of time (advantageously, between approximately 10 and 90 minutes). Although the mechanism for this is not yet precisely known, it is likely that the contrast agent does not enter living myocardial cells, but does enter dead myocardial cells via broken cell membranes. In the case of scar tissue, it may be that the contrast agent accumulates in the increased extracellular space of the collagen matrix. As a result, the precise location of infarcted tissue can be visualized in an MR image acquired e.g. 10 to 90 minutes after administration of the contrast agent; dead tissue will appear hyperenhanced in the image, while normal and injured tissue will not. In short, the invention proceeds from the realization that after a predetermined waiting period, myocardial regions hyperenhanced with MR contrast agent are exclusively dead. Thus, as a result of this discovery, infarcted tissue can be precisely localized using MRI, faster and with higher spatial resolution than a nuclear medicine study.
It should be noted that such a hyperenhanced region occasionally has an unenhanced subregion at its center. This unenhanced subregion is also infarcted and it only shows up as unenhanced because the contrast agent has not reached it at the time the MR study has been carried out.
Advantageously, and in accordance with the preferred embodiment, a T1-weighted MR pulse sequence (specifically a segmented T1-weighted inversion recovery turboFLASH implementation) is used to produce a T1-weighted MR image of the patient's heart. This makes the location of the contrast agent particularly apparent and makes it easier to identify infarcted tissue.
Once it is possible to identify infarcted tissue, it is then possible to distinguish between normal tissue and injured tissue even though both enhance identically in the MR image. This distinction can be drawn by using a cine MR study to determine regions of the myocardium that do not move normally during the cardiac cycle. If an abnormally moving region is hyperenhanced by contrast agent, the region is infarcted; if the abnormally moving region is not hyperenhanced, the region is injured. Normally moving regions indicate normal tissue.